Medical oncology
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Estrogen classically drives lung cancer development via estrogen receptor β (ERβ). However, fulvestrant, an anti-estrogen-based endocrine therapeutic treatment, shows limited effects for non-small cell lung cancer (NSCLC) in phase II clinical trials. G protein-coupled estrogen receptor (GPER), a third estrogen receptor that binds to estrogen, has been found to be activated by fulvestrant, stimulating the progression of breast, endometrial, and ovarian cancers. ⋯ Importantly, the pro-tumorigenic effects of GPER induced by E2 were significantly reduced by co-administering the GPER inhibitor G15 and the ERβ inhibitor fulvestrant, as compared to administering fulvestrant alone both in vitro and in vivo. Moreover, the phosphorylation of MAPK and Akt was involved in E2/G1-induced GPER activation. In conclusion, our results indicated that a pro-tumor function of GPER exists that mediated E2-/G1-dependent NSCLC progression and showed better efficiency regarding the co-targeting of GPER and ERβ, providing a rationale for further investigation of anti-estrogen clinical therapy.
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CCR9-CCL25 interaction suppresses apoptosis of lung cancer cells by activating the PI3K/Akt pathway.
CC chemokine receptor-9 (CCR9) is highly expressed in non-small cell lung cancer (NSCLC) tissues and cell lines. However, the biological functions and the signals elicited by the interaction between CCR9 and its natural ligand CCL25 in NSCLC are unknown. Here, we selectively depleted CCR9 and inhibited CCR9-CCL25 interaction in NSCLC cells using small recombinant lentivirus-mediated miRNA, and investigated the tumorigenic effects in vitro and in vivo. ⋯ In vivo studies also demonstrated a significantly lower tumor burden in mice receiving CCR9-silence cells than those in mice receiving control cells. Together, these data suggested that CCR9-CCL25 interaction induced tumorigenesis of NSCLC cells and that this induction might be accomplished through the activation of the PI3K/Akt pathway. These findings may lead to a better understanding of the biological effects of CCR9-CCL25 interaction and provide clues for identifying novel therapeutic and preventive molecular markers for NSCLC.
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The meta-analysis evaluated the efficacy and safety of chemotherapy or tyrosine kinase inhibitors combined with bevacizumab versus chemotherapy or tyrosine kinase inhibitors alone in the treatment of non-small cell lung cancer (NSCLC). The PubMed/MEDLINE, Ovid, Web of Science, CNKI, and the Cochrane Library database were searched for eligible randomized controlled trials comparing the combination of chemotherapy or epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) with bevacizumab to chemotherapy or EGFR-TKI alone. Main outcome measures were overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and adverse effects. ⋯ A higher incidence of grade ≥3 adverse events such as proteinuria, hypertension, and hemorrhage was observed in the bevacizumab combination group than in the control group without bevacizumab (P all < 0.05). The addition of bevacizumab to chemotherapy or erlotinib can significantly improve PFS and ORR both in first- and second-line treatments of advanced NSCLC, with an acceptable risk of bleeding events, hypertension, proteinuria, and rash. Combination therapy with bevacizumab and chemotherapy is beneficial regarding OS; however, whether bevacizumab plus erlotinib can prolong OS need further validation.
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Stage III/IV extranodal natural killer/T cell lymphoma (ENKL) has a poor response and poor survival. Given the sensitivity of ENKL to radiotherapy and the fact that there is no consensus on standard chemotherapy, we conducted a clinical trial of LVDP regimen, combining LVDP chemotherapy (containing etoposide, dexamethasone, L-asparaginase, and cisplatin), followed by radiotherapy as a consolidation therapy regimen, for newly diagnosed patients with stage III/IV ENKL to evaluate the efficacy and safety of this regimen. The primary endpoints were overall response rate (ORR) and survival [overall survival (OS) and progression-free survival (PFS)] at 1 or 2 years, while the secondary endpoints were toxicity and adverse effects. ⋯ During a mean follow-up of 21.8 months (range 2-51 months), the 1-year OS and PFS rates were 72.2 and 50.0 %, respectively, the 2-year OS and PFS rates were 33.3 and 22.2 %, respectively, and the median OS and PFS were 23.0 and 10.5 months, respectively. Severe adverse effects during therapy included six cases of grade 3/4 bone marrow suppression and one case of grade 3 transaminase increase. Sex, eastern cancer oncology group, performance status, Korean Prognostic Index, International Prognostic index, and bone marrow infiltration may influence the prognosis of advanced-stage ENKL.
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Case Reports
Rapid response of brain metastases to alectinib in a patient with non-small-cell lung cancer resistant to crizotinib.
Crizotinib is a potent and specific small-molecule inhibitor of both anaplastic lymphoma kinase (ALK) and c-MET tyrosine kinases, and patients with ALK rearrangement tumor benefit from crizotinib treatment; however, its penetration into calculated cerebrospinal fluid (CSF) is considered to be poor. Alectinib is a highly selective, next-generation ALK inhibitor, and both preclinical and clinical studies have indicated that alectinib is also effective in crizotinib-resistant tumors. ⋯ In this paper, we report a first case alectinib was highly effective against brain metastases refractory to crizotinib. Further investigation of alectinib in this setting would be particularly valuable.